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antimicrobial resistance publication research tuberculosis

New Publication: Structure of MmpL3

Oliver Adams successfully elucidated the structure of the M. tuberculosis MmpL3 membrane transporter using cryo-EM and this has recently been published online in Structure. This was the main aim of his PhD studies in Simon Newstead‘s group in the Department of Biochemistry here in Oxford. It is an important protein structure since although other MmpL3 […]

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antimicrobial resistance clinical microbiology publication

New preprint: Deciphering bedaquiline and clofazimine resistance in tuberculosis

In this preprint we examine 14,151 clinical isolates drawn from the CRyPTIC dataset. Each isolate had its minimum inhibitory concentration (MIC) to bedaquiline and clofazimine measured and hence we were able to identify the transcription regulator Rv0678, as the current main source of elevated MICs to both these drugs. Lindsay Sonnenkalb, who is studying for her […]

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antimicrobial resistance clinical microbiology publication research tuberculosis

New print: Epidemiological cutoff values for a 96-well broth microdilution plate for M. tuberculosis

In this preprint, the CRyPTIC project proposes the maximum value of minimum inhibitory concentration (MIC) for 13 different anti-TB drugs below which a sample can be considered to be ‘genotypically wild-type’. It is necessary to establish these values, called epidemiological cutoff values (ECOFFs or ECVs), so that the MICs measured can be converted into binary […]

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clinical microbiology publication

New publication: Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers

A second Covid-19 publication I’m proud to be (a small) part of has recently published been in the New England Journal of Medicine. Given the Oxford University Hospital’s Staff Covid testing has been running for months, as described in our first publication, the team was able to show that having antibodies led to a substantially […]

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antimicrobial resistance computing distributed computing GPUs molecular dynamics publication research

New publication: how quickly can be calculate the effect of a mutation on an antibiotic?

The idea for this paper arose during talking over coffee at the BioExcel Alchemical Free Energy workshop in May 2019. We’d previously shown that alchemical free energy methods could successfully predict which mutations in S. aureus DHFR  confer resistance to trimethoprim (and crucially, which do not). That is all well and good, but to do […]

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antimicrobial resistance clinical microbiology publication

New publication: Differential occupational risks to healthcare workers from SARS-CoV- 2

Very pleased and proud to be included on this manuscript, which has been published in eLife (and is also  available as a preprint); the observations are drawn from the large and comprehensive SARS-CoV-2 testing programme run by Oxford University Hospitals NHS Trust. I helped develop the internal website used by staff to book appointments and […]

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antimicrobial resistance clinical microbiology publication research

New publication: Reconciling the potentially irreconcilable? Genotypic and phenotypic amoxicillin-clavulanate resistance in Escherichia coli.

Clinical microbiology often assumes a sample is resistant or susceptible. Making such a classification relies on applying a threshold (usually called a cutoff) to quantitative data, such as minimum inhibitory concentrations (MICs). If the MICs are strongly bimodal, then this is trivial and reproducibility is guaranteed. If the MICs are unimodal, then one is left […]

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antimicrobial resistance clinical microbiology publication research tuberculosis

New publication: Phylogenetically informative mutations in genes implicated in antibiotic resistance in Mycobacterium tuberculosis complex

Although the population structure M. tuberculosis is clonal, one must be careful when inferring the effect of individual mutations on the effect of an antibiotic. Purely because a mutation appears to define a phylogeny does not mean it has no effect on the minimum inhibitory concentration. Read more here (Open Access).

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antimicrobial resistance clinical microbiology computing GPUs molecular dynamics publication research

New preprint: rapid prediction of AMR by free energy methods

The story behind this preprint goes back to the workshop on free energy methods run by BioExcel in Göttingen in May 2019. I gave a talk, based in part on the work I’d previously published showing how alchemical free energy methods are able to predict which mutations in S. aureus DHFR confer resistance to trimethoprim.

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antimicrobial resistance molecular dynamics publication

New publication: Predicting resistance is (not) futile

Our “First Reactions” article has been published in ACS Central Science. We discuss the paper, Predicting Kinase Inhibitor Resistance: Physics-Based and Data-Driven Approaches, by Matteo Aldeghi, Vytautas Gapsys and Bert de Groot, which is in the same issue of the journal. Aldeghi et al. apply a series of methods to try and predict the effect […]